Lung function and bronchial hyper-responsiveness 11 years after hospitalization for bronchiolitis.
Atopic infants hospitalized for wheezing not caused by respiratory syncytial virus (RSV) carry the highest risk for later asthma. In the present paper, early risk factors for later lung function abnormalities and for bronchial hyper-responsiveness (BHR) were evaluated in 81 children, hospitalized for bronchiolitis in infancy, at the median age of 12.3 years. The basic data, including data on atopy in children and viral aetiology of bronchiolitis, had been collected on entry to the study at less than 2 years of age. Lung function was studied by flow-volume spirometry (FVS), and BHR by methacholine and exercise challenge tests 11.4 years after hospitalization during infancy. RSV aetiology of bronchiolitis was associated with reduced forced vital capacity (FVC; 93.65% of predicted +/- 11.05 vs. 99.57%+/- 12.59, p = 0.009). Early sensitization to inhalant allergens (OR 12.59, 95% CI 2.30-68.77) and maternal smoking during pregnancy (OR 4.58, 95% CI 1.28-16.39) were associated with BHR to exercise, and early atopic dermatitis (OR 3.48, 95% CI 1.09-11.10) was associated with BHR to methacholine. RSV bronchiolitis was associated with a restrictive pattern of lung function. Early atopy and maternal smoking during pregnancy may play a role in the development and persistence of BHR.


Mycobacterial heat-shock proteins as carrier molecules.
We have previously shown that the priming of mice with live Mycobacterium tuberculosis var. bovis (Bacillus Calmette-Guérin, BCG) and immunization with the repetitive malaria synthetic peptide (NANP)40 conjugated to purified protein derivative (PPD), led to the induction of high and long-lasting titers of anti-peptide IgG antibodies, overcoming the requirement of adjuvants and the genetic restriction of the antibody response to the peptide (Lussow et al., Proc. Natl. Acad. Sci. USA 1990. 87:2960). This initial work led us to the following observations. BCG had to be live for priming to lead to the induction of anti-peptide antibodies. Surprisingly, priming with other living microorganisms which chronically infect the macrophage (e.g. Salmonella typhimurium and Leishmania major) also induced anti-peptide antibodies in mice immunized with PPD-(NANP)40 conjugate. It was, thus, hypothesized that molecules expressed during active infection and also known to be highly conserved between species, namely the heat-shock proteins (hsp), could mediate the T cell sensitization required for the production of anti-peptide antibodies. In fact, when the PPD protion of the conjugate was replaced by a highly purified recombinant protein corresponding to the 65-kDa (GroEL-type) hsp of M. bovis, this resulted in the production of anti-(NANP) IgG antibodies in BCG-primed mice, irrespective of the major histocompatibility complex-controlled responsiveness to the (NANP) sequence itself. Further, similar induction of anti-peptide antibody response was also obtained with a recombinant 70-kDa (DnaK-type) hsp of M. tuberculosis, but not with a small molecular mass (18 kDa) of M. leprae. Finally, an adjuvant-free carrier effect for anti-peptide IgG antibody production in BCG-primed mice, was also exerted by the GroEL hsp of Escherichia coli. This finding that hsp can act as carrier molecules without requiring conventional adjuvants is of potential importance in the development of vaccine strategies.


Completed audit cycle to explore the use of the STOPP/START toolkit to optimise medication in psychiatric in-patients with dementia.
Aims and method To explore the use of the STOPP/START toolkit in older psychiatric in-patients with dementia. Clinical records and current drug charts were reviewed against STOPP/START criteria for all in-patients (n = 86) on six specialist dementia wards. Benzodiazepines, antipsychotics and opiates were most commonly prescribed inappropriately. The most common unprescribed medication groups were statins, calcium supplements and vitamin D supplements. There was an overall reduction of 7% in comorbidities and 8% in the number of prescriptions. t-test showed a significant drop in average comorbidities between both audits, t(1) = 23.920, P = 0.027, and in average prescriptions per patient, t(1) = 28.808, P = 0.022. There was no difference in the number of patients receiving polypharmacy, t(1) = 7.500, P = 0.084, or receiving medication with a high risk of adverse drug reactions, t(1) = 6.857, P = 0.092. Clinical implications The STOPP/START toolkit highlighted the importance of collaborative working between doctors, clinical pharmacists and nursing staff, and could provide old age psychiatrists with a structured tool to identify inappropriate prescribing of non-psychiatric medications. Declaration of interests None.


The strategic skills of business continuity managers: putting business continuity management into corporate long-term planning.
Despite its rapid development in the last two decades, business continuity management (BCM) as a discipline and a profession is still regarded by many as an operational entity of management. Two main issues are discussed in this paper: the role of BCM in strategic management and the strategic skills of business continuity managers. These issues are crucial as they represent the role of BCM in high-level corporate management. The paper discusses the importance of BCM in the long-term planning of organisational success and the preservation of future competitiveness. Finally, salient points that underpin the importance of its role in sustaining organisational performance are addressed.


Clinical, Sociobiological, and Cognitive Predictors of ADHD Persistence in Children Followed Prospectively Over Time.
With increasing awareness that ADHD is chronically disabling, a burgeoning literature has examined childhood clinical indicators of ADHD persistence. This study investigates whether childhood factors reflecting biological risk and cognitive reserve have additive predictive value for the persistence of ADHD that is unique beyond childhood indicators of disorder severity. One-hundred thirty children with ADHD (mean age = 8.9 years, 75 % male) were followed into adolescence (mean age = 14.0 years). Childhood ADHD and co-morbidities were assessed via interviews with parents and teachers; parental psychopathology was assessed via parent interview; exposure to neurobiological and psychosocial adversity were indexed by parent questionnaire; and cognitive reserve was evaluated through children's performance on measures of IQ and executive functioning. Univariate analyses identified childhood inattention and hyperactivity-impulsivity, co-morbid oppositional defiant disorder, overall impairment, and paternal anxiety and depression as more prevalent amongst adolescents with persistent compared with remitted ADHD. Only child-level predictors remained significant in a final multivariate model. These results suggest that children who are most likely to experience persistent ADHD have a more severe clinical presentation in childhood, reflected by increased levels of inattention, oppositional behavior, and impairment. They also are more likely to have fathers with internalizing concerns, but these concerns do not uniquely predict ADHD persistence beyond child-level factors. Contrary to expectations, childhood adversity and cognitive functioning did not predict the course of ADHD.


Prospective multicentre evaluation of a novel, low-profile transapical delivery system for self-expandable transcatheter aortic valve implantation: 6-month outcomes.
We assessed the safety and efficacy of a novel low-profile, 22-Fr transapical delivery system together with the ACURATE neo™ resheathable transcatheter heart valve. This prospective, single-arm, multicentre study enrolled 60 patients with severe symptomatic aortic stenosis and high surgical risk ineligible for transfemoral access. Primary end points were 6-month mortality and procedural success. The mean age of patients was 79.8 ± 4.7 years, and the patients had severe comorbidities including coronary artery disease (71.7%), diabetes (38.3%), atrial fibrillation (30.0%) and chronic obstructive pulmonary disease (21.7%); logistic EuroSCORE-I, -II and the Society of Thoracic Surgeons (STS) scores were 20.9 ± 8.9%, 6.1 ± 5.0% and 4.3 ± 2.9%, respectively. A non-rib spreading approach using soft tissue retractors only was used in 88.3% of patients (n = 53). Resheathing and repositioning of transcatheter heart valve were performed in 6.7% of cases (n = 4); the device implantation time was 3 ± 2 min. Apical access site complications occurred in 1.7% (n = 1). Procedural success was 98.3% (n = 59), and procedural success in the absence of major adverse cardiac and cerebrovascular events at 30 days was 90.0% (n = 54). At 30 days, cardiovascular and overall mortality were 8.3% (n = 5), stroke rate was 1.7% (n = 1), and 17.2% of patients (n = 10) received a permanent pacemaker implant. No paravalvular leakage ≥2+ was observed, and the mean transvalvular gradient was 5.9 ± 2.7 mmHg. At 6 months, survival was 84.3% with sustained haemodynamic results. This study indicates safety and efficacy of transapical aortic valve implantation using a novel low-profile delivery system. High procedural success, short implantation times and a low rate of apical access site complications underline the favourable safety profile and ease of use. ClinicalTrials.gov: NCT02950428.


Transforming growth factor-beta family members are regulated during induced luteolysis in cattle.
The transforming growth factors beta (TGFβ) are local factors produced by ovarian cells which, after binding to their receptors, regulate follicular deviation and ovulation. However, their regulation and function during corpus luteum (CL) regression has been poorly investigated. The present study evaluated the mRNA regulation of some TGFβ family ligands and their receptors in the bovine CL during induced luteolysis in vivo. On day 10 of the estrous cycle, cows received an injection of prostaglandin F2α (PGF) and luteal samples were obtained from separate groups of cows (n= 4-5 cows per time-point) at 0, 2, 12, 24 or 48 h after treatment. Since TGF beta family comprises more than 30 ligands, we focused in some candidates genes such as activin receptors (ACVR-1A, -1B, -2A, -2B) AMH, AMHR2, BMPs (BMP-1, -2, -3, -4, -6 and -7), BMP receptors (BMPR-1A, -1B and -2), inhibin subunits (INH-A, -BA, -BB) and betaglycan (TGFBR3). The mRNA levels of BMP4, BMP6 and INHBA were higher at 2 h after PGF administration (P<0.05) in comparison to 0 h. The relative mRNA abundance of BMP1, BMP2, BMP3, BMP4, BMP6, ACVR1B, INHBA and INHBB was upregulated up to 12 h post PGF (P<0.05). On the other hand, TGFBR3 mRNA that codes for a reservoir of ligands that bind to TGF-beta receptors, was lower at 48 h. In conclusion, findings from this study demonstrated that genes encoding several TGFβ family members are expressed in a time-specific manner after PGF administration.


Relationship between parental hypertension and cardiometabolic risk factors in adolescents.
This study aimed to investigate the relationship between parental hypertension and cardiometabolic risk factors in adolescents. The authors analyzed data of 554 adolescents aged 13 to 19 years from the Korean National Health and Nutrition Examination Survey 2013. The associations between parental hypertension and cardiometabolic abnormalities in adolescents were evaluated through multivariate logistic regression. Parental hypertension was noted in 16.2% of participants. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for overweight (OR, 2.08; 95% CI, 1.01-4.28) and obesity (OR, 2.11; 95% CI, 1.09-4.07) were significantly higher in participants with parental hypertension. The adjusted ORs for abdominal obesity (OR, 2.36; 95% CI, 1.01-5.56), high blood pressure (OR, 3.05; 95% CI, 1.19-7.78), and elevated alanine transaminase defined as >35 IU/L (OR, 2.86; 95% CI, 1.03-7.95) were significantly higher in participants with parental hypertension. Prevention of cardiometabolic risk factors should be reinforced in the offspring of hypertensive parents.


Trauma Nurses' Experience With Decontamination: Opportunities for Improvement.
Trauma patients are unique in their potential for exposure to dangerous chemicals or material, placing staff in the emergency department (ED) or trauma unit at risk for exposure themselves. The purpose of this study was to describe one centers' trauma nursing experience with decontamination and to identify opportunities for improvement. This was a cross-sectional descriptive study of decontamination practices using an anonymous online survey of trauma nurses at a single Midwestern verified Level I trauma center and burn center. A total of 82 nurses completed the survey with a 48% response rate. Overall, 57% reported having had some previous decontamination training, with ED and air transport nurse's training, knowledge, and comfort level reported as the highest and inpatient trauma nurses the lowest. A significant association was found between ED nurses and feeling the surest about their safety when caring for exposed patients (χ = 19.908, p = .018) and between hazardous materials training and receiving communication about the patient's decontamination procedures during care (χ = 8.879, p = .031). Our results show that trauma nurse decontamination training and communication, as well as confidence in knowledge and safety, vary by nursing unit. The relatively low-volume high-risk scenario of trauma decontaminations likely contributes to inpatient nurses reporting of inadequate preparedness. This requires administrative commitment to ensure that all trauma nurses receive decontamination training in orientation, as well as ongoing continuing education, skill competency checks, and simulation training. Decontaminate communication is an essential requirement of all ED trauma team handoffs and medical record documentation.


Thin sample refractive index by transmission spectroscopy.
Transmission spectroscopy and a small number of refractometer index measurements are combined to provide refractive index measurements of transparent samples ~50 um thick at hundreds of wavelengths with absolute accuracies <1 x 10(-4). Key to the technique is the use of independent index measurements to circumvent the need for an independent thickness measurement of the sample. The method was demonstrated on glass samples where fits to Cauchy curves had RMS accuracies <3 x 10(-5) from 415 to 1610 nm. Issues that must be addressed to reach this level of accuracy are discussed.


Point-of-Care Ultrasound Is a Valuable Modality During Mass COVID-19 Vaccination Campaigns.
Coronavirus disease 2019 has become a widespread public health crisis across the globe, requiring multiple approaches to containment, treatment, and prevention. Vaccines are an important tool to prevent morbidity and mortality from this devastating virus. Ensuring direct administration of vaccines into target tissue helps provide an optimal immune response while decreasing unintended adverse effects. Point-of-care ultrasound can better assist clinicians to determine appropriate needle length and penetration level especially in special populations. Examples include patients who are obese, pregnant, or with refractory lymphedema, and those living in areas where needle supply is unstable or insufficient.


Production of phenolic acids in hairy root cultures of medicinal plant Mentha spicata L. in response to elicitors.
In this study, hairy root induction in leaf and stem explants of Mentha spicata using various Agrobacterium rhizogenes strains was established for the first time. Although inoculation of explants by immersion method resulted in tissue necrosis, direct injection of explants by all examined strains (A13,R318,A4,GMI 9534 and ATCC15834) was effective. All different parts of the stem were susceptible to A. rhizogenes infection. However, the middle and lower internodes showed a higher rate of transformation. Among the different strains, the strain A13 exhibited the highest infection efficiency (almost 75% of the explants). A13 and R318-infected hairy roots showed the highest biomass production (close to 60 mg/flask), while infection with GMI 9534 produced the highest content of phenolic acids. Finally, the effect of phytohormone elicitation on hairy root growth and phenolic acid biosynthesis was investigated. A substantial increase in root growth and phenolic acids accumulation was obtained followed by 0.3 mg L-1 IBA and 100 µM MeJA treatment, respectively.


Time-frequency analysis of pupil size modulated by global luminance, arousal, and saccade preparation signals using Hilbert-Huang transform.
Pupil size changes constantly and is mainly determined by global luminance signals. In addition, the pupil responds to various cognitive and arousal processes, with larger pupil dilation observed in higher levels of cognitive or arousal processing. Although these task-evoked pupillary responses are extensively used in the pupil research, pupil analysis focusing on the frequency domain, particularly in the context of arousal and cognitive modulations, is less established. Fourier Transform method (FFT) has been used to understand the modulation of task difficulty on pupil oscillations. However, physiological signals are often characterized as non-linear and non-stationary waves, and the conventional spectral analytical method with linearity presumption is less appropriate to reveal modulation dynamics between time and frequency. Here, we used Hilbert-Huang Transform (HHT) to examine the time-frequency modulations on pupil size regulated by arousal, cognitive, and global luminance signals. Consistent with previous research, using FFT, higher spectral densities were obtained with lower luminance background. Moreover, higher spectral densities were found in the high emotional arousal condition. With HHT, we further demonstrated temporal changes on amplitude spectrum and inter-trial phase coherence (ITPC) in each intrinsic mode function (IMF), with stronger amplitudes in higher IMFs (i.e., low frequencies). Moreover, although global luminance, arousal and saccade preparation modulated pupil oscillatory responses, the modulation pattern in different IMFs was different. Together, our results demonstrated dynamics between the time and frequency domain on pupil oscillatory responses, highlighting the importance of examining the time-frequency interactions in the context of various pupil modulations.


The increase of slaughter weight in gilts as a strategy to optimize the production of Spanish high quality dry-cured ham.
Crossbred pigs (n=120) from Duroc sires mated to Landrace x Large White dams, with a mean BW of 110.5+/-2.3 kg, were used to investigate the effect of increasing the slaughter weight of gilts with regard to that of the barrows on the production of high quality dry-cured hams from Spain (Teruel ham). There were 3 treatments: barrows slaughtered at 130 kg of BW (B), gilts slaughtered at 130 kg of BW (G1), and gilts slaughtered at 134 kg of BW (G2). Growth performance was similar for G1 and G2, and both consumed less feed (P<0.001) and had less BW gain (P<0.05) and better G:F (P<0.01) than B. Also, the B treatment showed thicker backfat (P<0.001) and covering fat over the gluteus medius (GM) muscle (P<0.05) than G1 or G2, but no differences in carcass fat were detected between G1 and G2. Loin and ham yields were similar for B and G2, and both were less than those for G1 (P<0.01). Treatment did not affect the proportion of carcasses with a minimum weight of 84 kg, but the percentage of carcasses with a minimum fat depth over the GM muscle of 18 mm and the percentage of carcasses that fulfill both requirements (as required for the Teruel ham trademark) were less for G1 than for B or G2 (P<0.001). Meat from B had greater (P<0.05) intramuscular fat content than meat from G1 with loin from G2 being intermediate. Thawing losses of the loins were greater (P<0.05) for B than for G2 with loins from G1 being intermediate. Shear force value was greater for meat from G1 than for that from G2 with meat from B being intermediate (P<0.05). Fat over the GM muscle from the B treatment was more saturated and had decreased PUFA/SFA ratio than that from G1 with fat from G2 being intermediate (P<0.001). Also, backfat from the B treatment showed decreased (P<0.01) PUFA proportion than backfat from G1 or G2. We conclude that increasing the slaughter weight of gilts by 4 kg with respect to that of barrows optimized the 2 criteria used for the selection of carcasses destined for the production of Teruel ham.


Spherical aberration correction in multiphoton fluorescence imaging using objective correction collar.
Multiphoton microscopy has evolved into a powerful bioimaging tool in three dimensions. However, the ability to image biological specimens in-depth can be hindered by sample spherical aberration and scattering. These two phenomena can result in the degradation of image resolution and the loss of detected multiphoton signal. In this work, we use the correction collar (for cover glass thickness) associated with a water immersion objective in an attempt to improve multiphoton imaging. In the two samples we examined (human skin and rat tail tendon), we found that while the improvement in image resolution was not visible qualitatively, the measured axial fluorescence or second harmonic generation signal profiles indicate that the use of the correction collar can help to improve the detected multiphoton signals. The maximum increases are 36% and 57% for the skin (sulforhodamine B fluorescence) and tendon (second harmonic generation) specimens, respectively. Our result shows that for in-depth multiphoton imaging, the correction collar may be used to correct for spherical aberration. However, each tissue type needs to be examined to determine the optimal correction collar setting to be used.


Ibuprofen causes reduced toxic effects of interleukin 2 administration in patients with metastatic cancer.
Metastatic cancer was treated with interleukin 2 and lymphokine-activated killer cells with the addition of the cyclooxygenase inhibitor ibuprofen in an attempt to reduce side effects in 13 patients (eight male and five female). Twenty-six patients treated with only interleukin 2 and lymphokine-activated killer cells formed the control group. After interleukin 2 administration, a significantly increased number of lymphokine-activated killer cells were transfused in ibuprofen-treated patients. Cytotoxic effects were not significantly different in the treated and untreated groups. With regard to cell phenotype, both groups of patients manifested significant activation of the immune system as measured by T10 and OK1a. Symptom scores were dramatically reduced in patients treated with ibuprofen. Temperature above 37 degrees C were rare. Ibuprofen did not significantly alter rate of response in this immunotherapy trial (38% vs 42%). Ibuprofen is now routinely used in all of our current immunotherapy trials.


Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques.
Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials. To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques. This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017. Patterns of treatment failure and overall survival following locoregional failure or distant metastasis. Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with oropharyngeal carcinoma negative for human papillomavirus or p16 (median survival, 36.5 vs 13.6 months; P = .007) but not after distant metastasis. Salvage surgery was associated with improved overall survival following locoregional failure (hazard ratio, 0.51; 95% CI, 0.34-0.77; P = .001); oligometastatic disease (1 vs ≥2 lesions: hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001) was associated with improved overall survival following distant metastasis. Overall survival after recurrence of HNSCC is influenced by the HNSCC subsite and human papillomavirus or p16 status, as well surgical and systemic interventions. An oligometastatic phenotype characterizes patients with solitary metastasis after chemoradiotherapy. These findings have important implications for clinical trial designs for HNSCC in the recurrent and oligometastatic setting.


Sebaceous adenoma arising in mature cystic teratoma of the ovary. Case report.
We report the case of a 44-year-old female with sebaceous adenoma arising in mature cystic teratoma of the ovary. The patient had a tumor in the left ovary; 125 x 90 x 70 mm. Microscopically, the tumor consisted of structures typical of dermoid cysts. However, large areas of sebaceous proliferation were found. These areas were comprised of sebaceous nodules with features similar to a sebaceous adenoma of the skin. Immunohistochemically, the tumor showed "wild-type" expression of p53 and low proliferative activity (Ki-67 index < 5%). To verify the possibility of Muir-Torre syndrome we performed immunohistochemical examination of DNA mismatch repair proteins expression. However, all four proteins examined (MSH2, MSH6, MLH1, PMS2) were positive. Sebaceous adenoma arising in mature teratoma of the ovary is rare. To the best of our knowledge, only six cases have been reported in the literature to date.


Staged lengthening and reconstruction for children with a leg-length discrepancy after excision of an osteosarcoma around the knee.
Children treated for osteosarcoma around the knee often have a substantial leg-length discrepancy at skeletal maturity. The aim of this study was to investigate the results of staged skeletal reconstruction after a leg lengthening procedure using an external fixator in these patients. We reviewed 11 patients who underwent staged reconstruction with either an arthroplasty (n = 6) or an arthrodesis (n = 5). A control group of 11 patients who had undergone wide excision and concurrent reconstruction with an arthroplasty were matched for gender, location, and size of tumour. We investigated the change in leg-length discrepancy, function as assessed by the Musculoskeletal Tumor Society Scale (MSTS) score and complications. A mean 5.2 cm (1.7 to 8.9) of lengthening was achieved. The mean MSTS scores significantly improved after staged reconstruction (p = 0.003) but were still worse than those of the control group (p = 0.049). However, the MSTS scores of the arthroplasty subgroup were comparable with those of the controls, although the extensor lag was greater and the range of movement was less. The patient group experienced more complications, but all of these resolved. Approximately 5 cm of lengthening and significant functional improvement can be achieved by staged reconstruction and lengthening, without major complications. Although it has limitations, this method of treatment seems to be a satisfactory surgical option for growing children with a significant leg-length discrepancy after excision of an osteosarcoma around the knee. Cite this article: Bone Joint J 2017;99-B:401-8.


Cost-effectiveness of audiometric screening of first-year preparatory pupils in Dhofar Region, Oman.
Audiometric screening was conducted in Dhofar region to study the magnitude of ear problems and cost-effectiveness of screening first-year preparatory-school children in Oman. None of the 1894 pupils had otitis media with effusion or sensory neuronal hearing loss. Six children (0.32%) had impacted wax, 4 (0.21%) chronic suppurative otitis media and 2 (0.11%) dry perforation of eardrum. In all, 14 children (0.74%) with suspected hearing impairment were referred to a specialist but only 2 attended. Physicians and nurses spent 8-10 minutes for ear examination per child for a yield of less than 1%. The screening expenditure was US$ 5 per pupil. As the prevalence of serious ear conditions was low, we conclude that expanding the audiometric screening of schoolchildren to first-year preparatory pupils is not cost-effective.


Immunoglobulin heavy chain gene polymorphisms in Italian patients with psoriasis and psoriatic arthritis.
A polymorphism of the switch region of the mu IgH gene (S mu) is associated with arthritis in English patients with psoriasis. In this study, Italian patients with psoriasis alone (PS) or psoriatic arthritis (PSA) were analysed by Southern blot using DNA probes for the S mu region and a hypervariable locus 5' of the joining (JH) region of IgH (5' JH). No association between PSA and IgH gene polymorphisms was found. However, an association was found between PS and a genotype of the 5' JH region (Fisher's P = 0.0002, RR = 27). Additional DNA markers around the S mu region may reveal more accurate markers for PS or PSA.


Hepatitis C virus NS3/4A protease blocks IL-28 production.
Type I interferons (IFNs), including IFN-α, -β, and -ω, play a critical role in innate immune responses against viral infection. IFN-λ, including IL-29, IL-28A, and IL-28B, recently identified as a new subfamily of IFN named type III IFN, has also been demonstrated to suppress virus replication in vitro and in vivo. However, the molecular mechanisms that regulate the induction of type III IFNs during viral infection remain elusive. Here, we demonstrate that IL-28 (IFN-λ 2/3) IFN production, similar to type I IFN, represents a primary and direct host response to HCV genomic RNA transfection. IL-28 (IFN-λ2/3) induction by HCV genomic RNA was dependent upon the activation of NF-κB and IRF3. We identified a minimal IL-28 promoter region consisting of putative NF-κB and IRF3-binding sites. Furthermore, we showed that HCV infection can inhibit HCV genomic RNA-induced IL-28 expression, and that the viral NS3/4A protease activity was responsible for this inhibitory effect. Our results present important evidence for the control of type III IFN response by HCV, and shed more light on the molecular mechanisms underlying the persistence of HCV infection.


Cultivating Fluorescent Flowers with Highly Luminescent Carbon Dots Fabricated by a Double Passivation Method.
In this work, we present the fabrication of highly luminescent carbon dots (CDs) by a double passivation method with the assistance of Ca(OH)₂. In the reaction process, Ca2+ protects the active functional groups from overconsumption during dehydration and carbonization, and the electron-withdrawing groups on the CD surface are converted to electron-donating groups by the hydroxyl ions. As a result, the fluorescence quantum yield of the CDs was found to increase with increasing Ca(OH)₂ content in the reaction process. A blue-shift optical spectrum of the CDs was also found with increasing Ca(OH)₂ content, which could be attributed to the increasing of the energy gaps for the CDs. The highly photoluminescent CDs obtained (quantum yield: 86%) were used to cultivate fluorescent carnations by a water culture method, while the results of fluorescence microscopy analysis indicated that the CDs had entered the plant tissue structure.


Vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay for platelet response to cilostazol.
Recent clinical trials have demonstrated that cilostazol, an antiplatelet drug competent to inhibit phosphodiesterase 3, is effective in secondary prevention of atherothrombosis including ischemic stroke, myocardial infarction, and peripheral arterial disease. However, there is no reliable assay for detection of the platelet response to cilostazol. We attempted to establish such an assay for clinical use. Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol was measured by a platelet VASP assay kit that has been widely used for monitoring platelet response to ADP receptor antagonists in clinical settings. We modified the kit and found the optimal conditions for detection of cilostazol-dependent VASP phosphorylation. The assay could detect the in vitro and in vivo platelet responses to cilostazol effectively in the presence of 50 nM PGE1. ROC analysis showed that our assay had 97% sensitivity and 75% specificity when blood drawn between 3 and 9?h after cilostazol ingestion was subjected to the assay. The assay results were verified by immunoblotting specific for VASP phosphorylation. Standard light transmission platelet aggregometry could not detect significant inhibition of agonist-induced platelet aggregation by cilostazol except for the in vitro effect of high concentrations of cilostazol. These results demonstrate that the platelet VASP assay can detect the platelet response to cilostazol with high sensitivity and specificity.


Wanted Plasmodium falciparum, dead or alive.
Mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. Recent clarifications on the definition of regulated or accidental cell death by The Nomenclature Committee on Cell Death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context of malaria drug resistance, considering lack of really new drugs in the pipeline. Deciphering the mechanisms of death may help in detection of new drug targets and the design of innovative drugs. However, classifications have been evolving rapidly since initial description of "programmed cell death", leading to some uncertainty as to whether Plasmodium cell death is accidental or regulated.


[Primary hypokalemic periodic paralysis. Presentation of 18 cases].
The clinical features of 16 males and 2 females with hypokalemic periodic paralysis (HPP) are presented. Five patients had familial HPP, 4 thyrotoxic HPP and 9 sporadic disease. The age of onset ranged from 6 to 42 years. Clinical pictures varied from paraparesis to severe quadriplegia. The disease onset was earlier in familial HPP (p < 0.05) while sporadic cases showed the most severe, albeit shorter paralysis (p < 0.05). On admission, serum potassium levels ranged from 1.5 to 3.3 mEq/L; they did not correlate with the severity of paralysis. Glucose-insulin provocation test was positive in 5/5 patients. Oral potassium chloride and amiloride were useful to prevent paralysis. Contrasting with reports from USA and Europe, in México, HPP is not exceptional, and should be considered in the differential diagnosis of acute paralysis.


The influence of hydration state on thermoregulation during a 161-km ultramarathon.
It is advised that individuals should avoid losing >2% of their body mass during exercise in order to prevent hyperthermia. This study sought to assess whether a loss of >2% body mass leads to elevations in core temperature during an ultramarathon. Thirty runners agreed to take part in the study. Body mass and core temperature were measured at the start, at three locations during the race and the finish. Core temperature was not correlated with percent body mass change (p = 0.19) or finish time (p = 0.11). Percent body mass change was directly associated with finish time (r = 0.58, p < 0.01), such that the fastest runners lost the most mass (~3.5-4.0%). It appears that a loss of >3% body mass does not contribute to rises in core temperature. An emphasis on fluid replacement for body mass losses of this magnitude during prolonged exercise is not justified as a preventative measure for heat-related illnesses.


Full-stream and part-stream ultrasound treatment effect on sludge anaerobic digestion.
The use of ultrasound as pre-treatment to improve anaerobic digestion of secondary sludge has been established as a promising technology. There are great differences between lab scale and full-scale devices, regarding the relationship between the disintegration achieved and the energy supplied. Based on economic aspects, most of the full-scale plants use partial-stream instead of the full-stream sonication, which affects biogas production and digestate dewatering characteristics. A laboratory scale operation combining ultrasound and anaerobic digestion (batch tests) has been performed, determining the relationship between the ratio of sonicated sludge fed and the methane production, SCOD removal and capillary suction time after 20-day anaerobic biodegradation, in order to check the possible benefits of part-stream versus full-stream sonication. Additional incubation was also evaluated, searching for an optimum process combining ultrasound and 24-h incubation pretreatment. Results showed that by sonicating fresh WAS at 25,700 kJ/kg TS biogas yield increased linearly with the percentage of sonicated WAS in the substrate, from 248 (control reactor) to 349 mL CH(4)/g VS (41% increase in full-stream sonication). By incubation (24 h, 55 degrees C), 325 mL CH(4)/g VS were obtained (31% increase), but the digestion of the soluble compounds generated during incubation of sonicated sludge appeared to be less degradable compared to those solubilised by ultrasound or incubation alone, which showed no benefit in combining both treatments. Post-digestion dewatering deteriorated for both part-stream and full-stream sonication, and CST values were constant (74% higher than the control digestate) from 30% to 100% sonicated sludge.


On-site semi-automatic calibration and registration of a projector-camera system using arbitrary objects with known geometry.
In the Shader Lamps concept, a projector-camera system augments physical objects with projected virtual textures, provided that a precise intrinsic and extrinsic calibration of the system is available. Calibrating such systems has been an elaborate and lengthy task in the past and required a special calibration apparatus. Self-calibration methods in turn are able to estimate calibration parameters automatically with no effort. However they inherently lack global scale and are fairly sensitive to input data. We propose a new semi-automatic calibration approach for projector-camera systems that - unlike existing auto-calibration approaches - additionally recovers the necessary global scale by projecting on an arbitrary object of known geometry. To this end our method combines surface registration with bundle adjustment optimization on points reconstructed from structured light projections to refine a solution that is computed from the decomposition of the fundamental matrix. In simulations on virtual data and experiments with real data we demonstrate that our approach estimates the global scale robustly and is furthermore able to improve incorrectly guessed intrinsic and extrinsic calibration parameters thus outperforming comparable metric rectification algorithms.


Low Soluble Fms-Like Tyrosine Kinase-1, Endoglin, and Endothelin-1 Levels in Women With Confirmed or Suspected Preeclampsia Using Proton Pump Inhibitors.
Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement. Measurements were only made once, at study entry between weeks 20 and 41 (median 33 weeks). PPI use was associated with lower sFlt-1 levels, with no change in placental growth factor levels, both when compared with all non-PPI users and with 80 gestational age-matched controls selected from the non-PPI users. No sFlt-1/placental growth factor alterations were observed in women using ferrous fumarate or macrogol while, as expected, women using antihypertensive medication displayed higher sFlt-1 levels and lower placental growth factor levels. The PPI use-associated decrease in sFlt-1 was independent of the application of antihypertensive drugs and also occurred when restricting our analysis to patients with hypertensive disease of pregnancy at study entry. PPI users displayed more cases with preexisting proteinuria, less gestational hypertension, and a lower number of neonatal sepsis cases. Finally, their plasma endoglin and endothelin-1 levels were lower while sFlt-1 levels correlated positively with both. In conclusion, PPI use associates with low sFlt-1, endoglin, and endothelin-1 levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia.


Histone Methyltransferase NSD2 Activates PKCα to Drive Metabolic Reprogramming and Lenalidomide Resistance in Multiple Myeloma.
Multiple myeloma cells undergo metabolic reprogramming in response to the hypoxic and nutrient-deprived bone marrow microenvironment. Primary oncogenes in recurrent translocations might be able to drive metabolic heterogeneity to survive the microenvironment that can present new vulnerabilities for therapeutic targeting. t(4;14) translocation leads to the universal overexpression of histone methyltransferase NSD2 that promotes plasma cell transformation through a global increase in H3K36me2. Here, we identified PKCα as an epigenetic target that contributes to the oncogenic potential of NSD2. RNA sequencing of t(4;14) multiple myeloma cell lines revealed a significant enrichment in the regulation of metabolic processes by PKCα, and the glycolytic gene, hexokinase 2 (HK2), was transcriptionally regulated by PKCα in a PI3K/Akt-dependent manner. Loss of PKCα displaced mitochondria-bound HK2 and reversed sensitivity to the glycolytic inhibitor 3-bromopyruvate. In addition, the perturbation of glycolytic flux led to a metabolic shift to a less energetic state and decreased ATP production. Metabolomics analysis indicated lactate as a differential metabolite associated with PKCα. As a result, PKCα conferred resistance to the immunomodulatory drugs (IMiD) lenalidomide in a cereblon-independent manner and could be phenocopied by either overexpression of HK2 or direct supplementation of lactate. Clinically, t(4;14) patients had elevated plasma lactate levels and did not benefit from lenalidomide-based regimens. Altogether, this study provides insights into the epigenetic-metabolism cross-talk in multiple myeloma and highlights the opportunity for therapeutic intervention that leverages the distinct metabolic program in t(4;14) myeloma. Aberrant glycolysis driven by NSD2-mediated upregulation of PKCα can be therapeutically exploited using metabolic inhibitors with lactate as a biomarker to identify high-risk patients who exhibit poor response towards IMiD-based regimens.


[Improvement of claw health of cattle in Switzerland].
The modern technique of cattle hoof care was founded by E. Toussaint Raven in 1977. Environmental risk factors on cattle claws altered in the past 43 years. The change from free ranging to indoor housing, the intensified feeding and the breeding towards traits of high performance have significantly increased the mechanical and chemical stress on the claws. In modern free-stalls, dairy cows are required to walk on hard flooring to feed, drink and get milked. Good hoof health is a basic requirement for cattle welfare. Professional and regular hoof trimming is still considered the most effective measure to promote hoof health in dairy cattle. In order to meet today's requirements and to promote claw health, the Swiss Hoof Trimmers Association (SKV), in collaboration with the Vetsuisse faculties, Universities of Berne and Zurich, and the Bovine Health Service (RGD, Bern) developed and described the Swiss technique of functional claw trimming. The aim was to establish a consistent method, which takes into account the size and bodyweight of the modern cow, the anatomical and physiological characteristics of their claws and includes adaptations counteracting very relevant diseases such as digital dermatitis. The result is a workflow described and illustrated with coloured pictures and consisting of five individual steps based on the technique of E. Toussaint Raven, Additionally, the upcoming Swiss national resource project on long-term improvement of claw health is presented in some detail. The key point of this project is the electronic documentation of clinical findings by the trained professional claw trimmers. This data will later (i) be used to assess the foot health of Swiss cows, (ii) allow to determine the prevalence of foot diseases of cattle in Switzerland and (iii) to monitor the effect of the implementation of foot health concepts. The aim of this work is to combine the findings from science and the practical experience of hoof trimmers in one method, to standardize the applied hoof care in Switzerland and to adapt it to today's hoof health requirements.


Methylation profile of induced pluripotent stem cells generated by integration and integration-free approaches.
The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e.g., plasmids, Sendai virus, synthetic mRNAs and recombinant proteins). To evaluate the contribution of the reprogramming process isogenic system should be utilized (Shutova et al., 2016) [2]. Isogenic iPSC lines, obtained in different ways can serve the ideal system to investigate DNA methylation changes. The data presented in this article report methylation profiles for iPSC lines derived from fibroblasts of a healthy donor and PARK8-associated Parkinson's disease patient via integrating (lentiviral transfection) and non-integrating (Sendai virus infection) reprogramming using an Illumina 450K Methylation BeadChip platform. The data on DNA methylation of neurons differentiated from iPSC lines are also provided here.


Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation.
A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.


Postdiskogram CT features of lidocaine-sensitive and lidocaine-insensitive severely painful disks at provocation lumbar diskography.
At lumbar diskography, intradiskal lidocaine can eliminate or reduce provoked diskogenic pain. The purpose of this study was to evaluate the postdiskogram CT features of lidocaine-sensitive and lidocaine-insensitive severely painful disks. Intradiskal lidocaine was injected at 182 severely painful levels in 111 patients. Clinical records/imaging studies were reviewed for response to intradiskal lidocaine (complete/substantial, partial, and no pain improvement), evidence of diskographic contrast leakage (fluoroscopic/CT images), and the overall postdiskogram CT appearance in these severely painful disks. The assessed traditional Dallas grade (degeneration/radial tear [RT]) was supplemented by identified postdiskogram CT features of annular derangement (annular gap [AG], RT into peripheral annular tear [PAT], isolated PAT, lamellar annular tear, free/attached annular fragments, bucket-handle tear, and peripheral annular pocket). Isolated degenerative changes (40%) and radial defects with or without degeneration (60%) subsets were noted. Dallas grade 3 degeneration was most commonly observed (69%) with increased features of annular derangement in disks with a worsening Dallas grade. Complete/substantial versus no pain improvement was significantly associated with disk state (diskographic leakage, contained), radial defect (none, RT, or AG), and "RT-into-PAT" and were statistically significant in univariate models (P < .001). The associations remained significant in multivariate models. Higher Dallas degenerative grade and presence of free annular fragments were associated with a greater chance of no pain relief. Severely painful disks demonstrated complex annular derangement with both radial defects (RTs and AGs) or degenerative changes present, alone or in combination. Complete/substantial pain improvement after lidocaine administration is associated with disk state, radial defect (RT and AG), and RT-into-PAT.


Chronic diffuse infiltrative lung disease. Newer approaches.
A new scheme for description of diffuse infiltrative lung diseases using the graphic terminology of the International Labour Office Classification is described. Conventions for grading the type (rounded, or "pqr," and irregular, or "stu"), severity (profusion in 12 steps), localization of opacities, and pleural disease were retained. Modifications included (a) a third group of opacities, called "xyz," corresponding to reticulonodular patterns; and (b) "ground glass" (alveolar) patterns, subdivided into seven types by character and location. In a study of 365 cases proven by open biopsy, when this scheme was used without any knowledge of clinical data, the first two radiologic diagnostic choices corresponded with the principal histologic diagnosis in 50 per cent of cases. This classification provides an understandable and quantifiable system of communication and a tool for teaching, clinical research, and epidemiologic studies.


Angiogenesis and progesterone receptor status in primary breast cancer patients: an analysis of 158 needle core biopsies.
Formation of new blood vessels from a preexisting vascular bed (angiogenesis) is a complex multistep process, which may also permit metastasis. Progesterone receptor is a surrogate marker for ER activity and has been used as an additional predictive factor for hormonal therapy in breast cancer. To investigate how tumor angiogenesis correlates with progesterone receptor (PR) status in breast carcinoma diagnosed on core biopsy, microvessels were counted (and graded the density of microvessels) within the initial invasive carcinomas of 158 patients. Using light microscopy, the number of microvessels was counted manually in a subjectively selected hot spot (in the most active areas of neovascularization per 400x field), and their values were separated as above or below median (low and high), without knowledge of the outcome in the patient or any other pertinent variable. When the mean values of MVD of the various groups defined by PR status were compared, significant difference was noted (P = 0.008557). When tumors were classified as high or low MVD, based on a cut-off value (30.70175 microvessels/mm(2)), cases with high MVD were significantly more numerous. MVD did show a relationship with groups defined by PR status (P = 2.03076E-05). The correlation of angiogenesis with PR status may be a potential therapeutic target for the treatment and prevention of breast cancer, using antiangiogenic molecules.


Immune interactions at the maternal-fetal interface.
Models of murine allogeneic pregnancy have established that maternal T cells recognize fetal alloantigens and are normally suppressed or deleted. While the precise cellular interactions and mechanisms involved in maternal lymphocyte tolerance are not yet clear, the identity of some of the critical factors are beginning to be uncovered. Signals that have been shown in mice to have an obligatory role in immunological survival of the semiallogeneic fetus include, but are probably not limited to, indoleamine-2,3-dioxygenase and the newly discovered B7 family protein, B7-H1. Whether these proteins have intersecting functions is unknown, but it is possible that both are involved in the control of maternal T regulatory cells, which are also strictly required for successful allogeneic pregnancy in mice. Additional factors that are involved include trophoblast and/or maternally derived FasL, and in humans, class Ib HLA molecules. The potency of these mechanisms in protecting the fetal allograft is underscored by the scarcity of knockout and transgenic models in which pregnancy is immunologically compromised. Here, the current understanding of mechanisms of specific suppression of maternal lymphocytes is reviewed.


IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity.
Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.


Anticancer therapies and CNS relapse: overcoming blood-brain and blood-cerebrospinal fluid barrier impermeability.
Prolonged survival with targeted therapies has sometimes come at the expense of an increased risk of CNS relapse; because many of these agents poorly penetrate the BBB, malignant cells may remain viable within the CNS. The ability of anticancer drugs to penetrate the BBB is a major consideration in the treatment of CNS parenchymal metastases. Optimal chemotherapy approaches for treating CNS metastases remain unclear due to a lack of evidence-based recommendations. Recent hypothesis-generating studies evaluating intra-cerebrospinal fluid administration of targeted agents indicate that these drugs may be effective in treating leptomeningeal disease and are associated with a low incidence of drug-related adverse events. Newer strategies for treating cerebrospinal fluid metastases may co-opt endogenous systems of the BBB, such as those involved in receptor-mediated transcytosis or classic carrier-mediated transporter systems to facilitate drug delivery across the BBB.


Sudden breakdown in linear response of a rotationally driven magnetic microparticle and application to physical and chemical microsensing.
In this work, sensing magnetic microparticles were used to probe both the local pH and the viscosity-dependent nonlinear rotational behavior of the particles. The latter resulted from a critical transition marking a driven particle's crossover from phase-locking to phase-slipping with an externally rotating magnetic field, i.e., a sudden breakdown in its linear response that can be used to measure a variety of physical quantities. The transition from simple rotation to wobbling is described both theoretically and experimentally. The ability to measure both chemical and physical properties of a system could enable simultaneous monitoring of chemical and physical interactions in biological or other complex fluid microsystems.


Laparoscopic versus open radical hysterectomy in FIGO 2018 early-stage cervical adenocarcinoma: Long-term survival outcomes after propensity score matching.
To compare the long-term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early-stage cervical adenocarcinoma. Based on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early-stage cervical adenocarcinoma were retrospectively reviewed. Long-term and short-term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log-rank method in the whole study population and after propensity score matching. There was no difference in disease-free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532-1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526-2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk-adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk-adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613). LRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early-stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.


Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms.
A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In addition, novel gene targets of TW were identified using DNA microarray and quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3-TxR and DU145-TxR cells, respectively with Dtx IC50 reversed back to that of the sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity and induced a significant gene expression changes in genes related to angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo studies demonstrate that TW in combination with Dtx was able to overcome the chemoresistance and suppress resistant prostate tumor growth via multi-mechanisms.


Sport and exercise medicine - a new specialty.
Sport and exercise medicine (SEM) incorporates a diverse range of disciplines. These include: disease and injury prevention, management of medical problems in exercising individuals, management of soft tissue injuries sustained during exercise, and exercise prescription for improving physical fitness and treating disease.


Distribution of hearing loss characteristics in a clinical population.
This study was designed to characterize a large database of audiometric records from an academic health center Audiology clinic for the purpose of determining the distributions of hearing loss configuration, severity, and site of lesion. : Using AMCLASS, a validated tool for classifying audiograms described in a previous report, the audiometric configuration, severity, and site of lesion was determined for patients grouped according to the completeness of the audiometric record. Complete air conduction testing at six octave frequencies in both ears was required for inclusion. Patients were grouped according to the quantity of bone conduction thresholds in the record: both ears tested, one ear tested, or neither ear tested. All other records were discarded leaving 23,798 records of 16,818 patients for analysis. All analyses were conducted for all remaining records and with repeat tests excluded. The effect of removing repeat audiograms had remarkably little effect on the distributions. Sloping hearing losses dominated the distributions of configuration. One-third of all records indicated normal hearing in at least one ear and one fourth had normal hearing in both ears. Mild and moderate hearing losses were equally prevalent, each contributing 40% to 45% of the cases with hearing loss. Sensorineural was the most prevalent site of lesion, representing about 45% of cases and just over half the cases with hearing loss. Prevalence rates of hearing loss configurations, severities, and sites of lesion are provided against which analyses of other databases can be compared. The results may be useful for counseling patients regarding the relationship of their hearing loss to that of a large population. The high number normal-hearing people in the database suggests that estimates of the need for hearing testing based on prevalence of hearing loss may underestimate the number of people who seek or are referred for hearing evaluation.


Response to hepatitis B vaccine in HIV-1-positive subjects who test positive for isolated antibody to hepatitis B core antigen: implications for hepatitis B vaccine strategies.
Whether human immunodeficiency virus type 1 (HIV-1)-positive subjects who test positive for isolated antibody to hepatitis B core antigen (anti-HBc) should be vaccinated with hepatitis B vaccine is not certain. Development of an anamnestic response after vaccination would suggest previous hepatitis B virus (HBV) infection, in which case vaccination is not necessary. Sixty-nine HIV-1-positive subjects who tested negative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) received vaccination with standard hepatitis B vaccine. Twenty-nine subjects (42%) tested positive for anti-HBc, and 40 (58%) tested negative for anti-HBc. An anamnestic response was defined as an anti-HBs titer of >or=10 IU/L within 4 weeks of the first vaccination. The overall anamnestic response rate was 16% and was not significantly different between subjects who tested positive for anti-HBc (24%) and those who tested negative for anti-HBc (10%) before vaccination (P=.18). Approximately 50% of subjects who tested positive for anti-HBc also tested positive for antibody to hepatitis Be antigen (anti-HBe). The anamnestic response rate was higher in subjects who tested positive for both anti-HBc and anti-HBe (43%) than in subjects who tested positive for anti-HBc but negative for anti-HBe (7%) (P=.035). After a complete series of vaccinations, HIV-1/hepatitis C virus (HCV)-coinfected subjects were less likely to achieve high anti-HBs titers than were subjects infected with HIV-1 alone. After hepatitis B vaccination, the anamnestic response rate in HIV-1-positive subjects who tested positive for isolated anti-HBc but negative for anti-HBe was low and was comparable to that in subjects who tested negative for anti-HBc. This finding suggests that testing for anti-HBc alone may not be a reliable assessment of protection from HBV infection. HIV-1/HCV coinfection may be associated with impaired responses to hepatitis B vaccine, and evaluation of strategies to improve immunogenicity of the vaccine in such individuals is warranted.


Strain topography of human tendon and fascia.
Discretized surface strains for human tendon and fascia were photogrammetrically determined with high-speed cinematography and were displayed topographically using three-dimensional computer graphics. Substantial differences were found between estimates of tissue strain measured from grip motion versus discretized strain estimates from high-speed films. The computer-generated contour maps also provide a useful technique for analyzing the nonhomogeneity of tendon and fascial strains during high rate tests.


Protective effects of sucralfate and omeprazole on gastric mucosal damage induced by ethanol in rats.
Studies on the protective effect of omeprazole, a proton-pump inhibitor, against damage to the rat gastric mucosa induced by strong irritants, are few and contradictory. We have investigated the protective effects of omeprazole and sucralfate against gastric mucosal damage induced by ethanol in rats. The study was performed on 4 groups of 10 rats each. Group A received omeprazole 7 mg/kg/day intraperitoneally (i.p.) for 7 days. Group B received an equivalent volume of 0.9% sodium chloride i.p. for 7 days, while no drugs were given to groups C and D. After 1 week, following 24 hours of fasting, group A received omeprazole 7 mg/kg, group B received an equivalent volume of 0.9% sodium chloride group C received omeprazole 7 mg/kg i.p. and group D received sucralfate, 100 mg/kg intragastrically (i.g.). 4 hours after groups A, B and C received the last medication and 30 minutes after group D received sucralfate, ethanol 95% was given i.g. All rats were sacrificed 1 hour after ethanol application and their stomachs were removed for macroscopic and microscopic examination. It was found that sucralfate was effective in preventing gastric lesions induced by ethanol. There was a significant difference between the sucralfate group and the other group (p < 0.001). Omeprazole was ineffective in preventing gastric lesions, either given as a single dose or after administration for 7 days. Our results indicate that sucralfate has a protective effect on gastric lesions induced by ethanol and omeprazole applied i.p. has no protective effect.


Whatever Happened to Measuring Ventricular Contractility in Heart Failure?
Attempts have been made to assess and measure ventricular contractility in patients and whether it can be used to identify heart failure. Due to the assumption that if the contractility of all the muscle fibres in a heart were lower, could it be called heart failure? Early attempts involved the assumption of a model of muscle that had a contractile unit in series with an elastic element, but this was found to be incorrect. Further attempts applied the series elastic model but this model also proved challenging. However, one method has assessed changes in contractility in a given patient, in response to an intervention, but could not compare contractility in a patient with heart failure with a normal person. End-systolic pressure-volume (ESPV) is regarded as a more correct index of contractility and this method was used to confirm changes in contractility from beat to beat during AF, showing results that end-systolic volume varied and indicating a shift of ESPV from beat to beat. This review will discuss the difficulty in measurement, the complicated nature of myocardial fibre orientation and hypertrophy, and whether myocardial contractility failure precipitates increased global heart failure.


Blocking the Cycle: Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic, Hormone Receptor-Positive Breast Cancer.
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old postmenopausal woman was diagnosed with breast cancer 6 years ago when she presented with a stage II (T2N1), right-sided, invasive ductal carcinoma considered grade 2 of 3 on core biopsy, with a positive fine-needle aspiration of a palpable, ipsilateral axillary lymph node. Immunohistochemical analysis was positive for estrogen and progesterone receptor expression and negative for human epidermal growth factor receptor 2 (HER2) overexpression. She received neoadjuvant dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy, followed by breast-conserving surgery and axillary lymph node dissection, which revealed residual disease in three of 11 nodes. She received adjuvant radiation therapy and initiated letrozole, with excellent compliance during the interval 6-year period. While receiving adjuvant letrozole therapy, she reported 3 months of worsening back pain. Skeletal scintigraphy and cross-sectional imaging confirmed widespread osseous metastatic disease and right supraclavicular lymph node enlargement ( Fig 1 ). Core biopsy of the involved lymph node confirmed estrogen receptor (ER)-positive (90%), progesterone receptor-negative, HER2-negative recurrent metastatic breast cancer. The patient reported mild pain that was adequately controlled with over-the-counter anti-inflammatory medications. She has remained active with an excellent performance status.


A qualitative analysis of trust and distrust within patient-clinician interactions.
Trust represents a key quality of strong clinician-patient relationships.1 Many have attempted to assess patient-reported trust. However, most trust measures suffer from ceiling effects, with no variability, making it not possible to examine predictors of trust and distrust. Rather than rely on patient reports, we created a codebook for instances of trust and distrust from actual patient-clinician encounters. Three coders conducted a qualitative analysis of audio recordings among patient-cardiologist outpatient encounters. We identified trust and distrust based on vocal and verbal cues in the interactions. We found consistent patterns that indicated patient trust and distrust. Overall, this work empirically validates a new more accurate measurement of trust for patient-doctor interactions. We are the first to use audio recordings to identify verbal markers of trust and distrust in patient-clinician interactions. From this work, others can code trust and distrust in recorded encounters rather than rely on self-report measures.


Features of liver tissue remodeling in intestinal failure during and after weaning off parenteral nutrition.
Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition. Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6.3 years (2.4-17) earlier, after having received parenteral nutrition for 10 months (3.3-34). Expression of alpha-smooth muscle actin, collagen 1, proinflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was measured. Significant increases in immunohistochemical expression of alpha-smooth muscle actin and collagen 1 were observed predominantly in portal areas and were similar to increases seen in patients currently receiving parenteral nutrition and in patients weaned off parenteral nutrition. Gene and protein expressions of alpha-smooth muscle actin and collagen were interrelated. Gene expression of ACTA2, encoding alpha-smooth muscle actin, was increased only in patients who were receiving parenteral nutrition currently. Comparable upregulation of interleukin-1 (α and ß), epidermal growth factor, integrin-ß6, and MMP9 gene expression was observed in both patient groups, irrespective of whether they were receiving parenteral nutrition currently. Liver expression and serum levels of TIMP1 and MMP7 were increased only in the patients on parenteral nutrition currently but were not increased after weaning off parenteral nutrition. Intestinal failure is characterized by abnormal activation of hepatic myofibroblast and accumulation of collagen both during and after weaning off parenteral nutrition. Persistent transcriptional upregulation of proinflammatory and fibrogenic cytokines after weaning off parenteral nutrition suggests that factors other than parenteral nutrition may contribute to intestinal failure-associated liver disease.


Traumatic retroperitoneal venous haemorrhage.
Vena caval injury is rare in the UK, but changes in society suggest that it may become more frequent. The problem is always unexpected and presents a major surgical challenge. Modern techniques have led to a substantial improvement in survival so that most patients with an infrarenal injury should now survive but only with prompt, effective treatment. In this review the problems and techniques of surgical management are illustrated by three cases of traumatic injury and two of peroperative accidents.


The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss.
Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1-/-E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.


Differentiation of Benign and Malignant Parotid Gland Tumors with MRI and Diffusion Weighted Imaging.
This study investigated the effectivity of Magnetic Resonance Imaging (MRI) findings and Apparent Diffusion Coefficient (ADC) value in evaluating parotid gland tumors (PGTs), and aimed to reduce the biopsy procedure before surgery. This retrospective study included 54 PGTs of 42 patients' (24 female, 18 male, mean age; 51.4±15.9). All of the patients had an MRI, and histopathologic diagnosis. The signal intensity [T1 and T2 Weighted (W), T1W after intravenous contrast agent injection] and mean ADC values of the PGTs were measured. Also contrast enhancement pattern (homogenous, heterogeneous, peripheral or none), margin features (well or ill-defined), sizes, location (superficial lobe/deeplobe/both), perineural spread, presence of lymphadenopathy, and extension to adjacent structures were noted. The distribution of PGTs was; 21 pleomorphic adenomas, 18 Warthin tumors, 2 lymph nodes, 2 mucoepidermoid carcinomas, 5 adenoid cystic carcinoma, 1 basal cell carcinoma,2 metastases and 2 lymphomas; (13 malignant and 41 benign lesions). Morphologic parameters; ill-defined margin, perineural spread, lymphadenopathy, and extension to adjacent structures were found to be significantly associated with malign lesions (p<0.01). There was a significant difference between ADC values of malignant and benign PGTs (p<0.05). Also ADC values and T2 signal intensity was significantly lower in Warthin tumors rather than pleomorphic adenomas (p<0.05). Mean ADC values when considered with morphological features may be accessible methods to distinguish benign and malignant PGTs, also ADC values and T2 signal intensity may be useful for differentiating pleomorphic adenomas from Warthin tumors, thereby reducing the number of biopsies and thus complications.


Using RNA-based therapies to target the kidney in cardiovascular disease.
RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular homeostasis, many extant drugs used for preventing cardiovascular disease act predominantly on renal tubular cells. Moreover, kidney disease is a major independent risk factor for cardiovascular disease and a global health problem. Chronic kidney disease is projected to become the fifth leading cause of death by 2040, with around half of affected individuals dying from cardiovascular disease. The most promising strategies for delivering therapeutic RNA selectively to kidney cells make use of synthetic polymers and engineered extracellular vesicles to deliver an RNA cargo. Future research should focus on establishing the safety of these novel delivery platforms in humans, on developing palatable routes of administration and on prioritising the gene targets that are likely to have the biggest impact in cardiovascular disease.


Excess mortality during hospital stays among patients with recorded diabetes compared with those without diabetes.
To assess the additional mortality during hospital admissions among patients with recorded diabetes and identify the extent of variation in English provider trusts. Inpatient admissions to all English hospitals between April 2010 and March 2012 were extracted from Hospital Episode Statistics. Binary logistic regression was used to standardize for age, sex, deprivation, method and reason for admission, co-morbidities and type of trust. Trust level standardized mortality ratios for inpatients with recorded diabetes were compared with those without recorded diabetes and with published measures of hospital mortality. Of the 10 169 003 hospital admissions analysed, 11.2% had recorded diabetes, but 21.5% of inpatient deaths occurred in this group. After adjustment for case mix, hospital admissions in patients with recorded diabetes had a 6.4% greater risk of dying (2052 more deaths over 2 years) than would be expected compared with similar patients without recorded diabetes. The additional risk of death was significantly greater in smaller trusts. The highest additional risk of death was found in hospital admissions of younger female patients admitted electively. At provider trust level, 37.4% of variation in adjusted mortality in patients with recorded diabetes was explained by the mortality in those without recorded diabetes. A diagnosis of diabetes has an adverse impact on hospital mortality that cannot be explained by usual case-mix adjustments, and the additional risk of dying is greatest among hospital admissions that would normally have a low risk of death. This implies that diabetes may override the usual risk factors for hospital mortality.


Lanthanoid "bottlebrush" clusters: remarkably elongated metal-oxo core structures with controllable lengths.
Large metal-oxo clusters consistently assume spherical or regular polyhedral morphologies rather than high-aspect-ratio structures. Access to elongated core structures has now been achieved by the reaction of lanthanoid salts with a tetrazole-functionalized calixarene in the presence of a simple carboxylate co-ligand. The resulting Ln19 and Ln12 clusters are constructed from apex-fused Ln5O6 trigonal bipyramids and are formed consistently under a range of reaction conditions and reagent ratios. Altering the carboxylate co-ligand structure reliably controls the cluster length, giving access to a new class of rod-like clusters of variable length.


Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues.
Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-induced VA are poorly understood. This review will discuss the ventricular conduction (QRS) and repolarisation abnormalities (QTc prolongation), and VAs associated with cancer therapies, as well as existing strategies for the identification, prevention and management of cancer-treatment-induced VAs.


A small angle x-ray scattering study of a fragment derived from E. coli 5S RNA.
The structure of a 62 base nuclease resistant fragment of E. coli 5S RNA (bases 1-11, 69-87, 89-120) has been examined by small angle x-ray scattering. The results obtained are indistinguishable from those expected if this oligonucleotide complex were a perfect RNA double helix of about 30 base pairs. These results indicate that this portion of 5S RNA is in a configuration which is approximately double helical, even though proper base pairing is possible over only half its length.


Computationally-assisted approach to the vibrational spectra of molecular crystals: study of hydrogen-bonding and pseudo-polymorphism.
A new computationally-assisted methodology (PiMM), which accounts for the effects of intermolecular interactions in the crystal, is applied to the complete assignment of the Raman and infrared vibrational spectra of room temperature forms of crystalline caffeine, theobromine, and theophylline. The vibrational shifts due to crystal packing interactions are evaluated from ab initio calculations for a set of suitable molecular pairs, using the B3LYP/6-31G* approach. The proposed methodology provides an answer to the current demand for a reliable assignment of the vibrational spectra of these methyl-xanthines, and clarifies several misleading assignments. The most relevant intermolecular interactions in each system and their effect on the vibrational spectra are considered and discussed. Based on these results, significant insights are obtained for the structure of caffeine in the anhydrous form (stable at room temperature), for which no X-ray structure has been reported. A possible structure based on C((8))--H...N((9)) and C((1,3))--H...O intermolecular interactions is suggested.


A novel and effective technique to reduce electromagnetic radiation absorption on biotic components at 2.45 GHz.
A strong evidence of the effects of radiation absorption on the living community together with a better solution to reduce the radiation intensity without compromising the usage of wireless communication systems is presented. This study analyses the radiation effects on living things and validates the proposed techniques for specific absorption rate (SAR) value reduction at 2.45 GHz. To reduce these radiation impacts on the living community, proper shielding from the radiation and effectively reorienting antenna radiation patterns are the solutions suggested. An analogous antenna configuration in wireless communication systems - a coplanar waveguide fed loop antenna is considered and an open loop resonator (OLR) optimized in ANSYS HFSS at 2.45 GHz is incorporated on the back side of the proposed antenna for achieving SAR value reduction. Theoretical and experimental validation is carried out by measuring the variation in absorption power on each vegetable sample using vector network analyzer E5080A. The existence of OLR on the back side of the antenna reduces the absorption power upto 2 dB. From experimental validation, the proposed technique provides 88% to 98% reduction in SAR value when tested in each sample. Along with this OLR exhibits the capability to enhance the shielding characteristics to the controlled environment of experimental setup for analyzing the stages of seed germination, which helps in reducing the reported radiation effects and growth retardation. The proposed method of EMR reduction with miniaturized planar resonator can be effectively used in the communication systems operating at 2.45 GHz for creating a reduced radiation environment.


Biogeography meets taxonomy: Distribution-based inferences on the accuracy of identification and synonymization of East Asian earthworms.
This paper demonstrates that the uniqueness of the geographical location of Taiwan and its adjacent islands can be taken as a basis to evaluate the accuracy of identification and synonymization of East Asian earthworms and further to clarify some disputes in earthworm taxonomy. A comprehensive review of the earthworm fauna from the Ryukyu Archipelago is given; as a result, two recorded species are recognized as new species, named here Amynthas ishigakiensis sp. nov. and Amynthas iriomotensis sp. nov. Common but harmful practices in earthworm taxonomy, synonymies with question marks and erection of sympatric subspecies, are commented.


Cleanliness in context: reconciling hygiene with a modern microbial perspective.
The concept of hygiene is rooted in the relationship between cleanliness and the maintenance of good health. Since the widespread acceptance of the germ theory of disease, hygiene has become increasingly conflated with sterilization. In reviewing studies across the hygiene literature (most often hand hygiene), we found that nearly all studies of hand hygiene utilize bulk reduction in bacterial load as a proxy for reduced transmission of pathogenic organisms. This treatment of hygiene may be insufficient in light of recent microbial ecology research, which has demonstrated that humans have intimate and evolutionarily significant relationships with a diverse assemblage of microorganisms (our microbiota). The human skin is home to a diverse and specific community of microorganisms, which include members that exist across the ecological spectrum from pathogen through commensal to mutualist. Most evidence suggests that the skin microbiota is likely of direct benefit to the host and only rarely exhibits pathogenicity. This complex ecological context suggests that the conception of hygiene as a unilateral reduction or removal of microbes has outlived its usefulness. As such, we suggest the explicit definition of hygiene as "those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease."


[Changes of lipid metabolism in patients with chronic viral hepatitis treated with interferon alpha].
Changes of lipid metabolism are often observed in patients (pts) with chronic viral hepatitis during interferon therapy. Many studies show changes in blood lipids including increase of triglycerides level, decrease of total cholesterol as well as HDL lipoprotein levels. This study was an attempt to widen our knowledge about additional factors responsible for changes in lipid metabolism of pts with chronic viral hepatitis during interferon therapy. The aim of this study was to assess the changes of total cholesterol, triglycerides and LDL-, HDL-lipoproteins levels in blood serum in comparison to: activity of hepatic inflammation, degrees of fibrosis, type of hepatotropic viruses and response to antiviral treatment. In the group of 53 pts (18 female, 35 male), age 16-61 years old with chronic hepatitis B (13 pts) and chronic hepatitis C (40 pts) treated with interferon alpha we examined the cholesterol, HDL, LDL-lipoproteins and TG levels in blood serum at the beginning of therapy and in the sixth month. Changes of lipids values at the beginning and in the sixth month of therapy were assessed in respect to: necro-inflammatory changes of the liver in histopathological examination, degrees of fibrosis, obesity, loss of the weight during IFN therapy, response to treatment, type of hepatotropic viruses (HBV, HCV), sex and age. During sixth month of interferon therapy there was significant decrease of total cholesterol level (before treatment 4.1 +/- 1.0, after treatment 3.8 +/- 0.9, p < 0.05) and HDL-lipoproteins level (before treatment 1.3 +/- 0.35, after treatment 1.1 +/- 0.35, p < 0.05). Increase of TG level was not statistically significant. The necro-inflammatory changes in the liver correlated with the values of TG level. Low activity of hepatic inflammation correlated with the increased TG level at sixth month of therapy. There was not observed effect of any other factors on the lipid metabolism.


Azole resistance in Candida albicans from animals: Highlights on efflux pump activity and gene overexpression.
This study investigated potential mechanisms of azole resistance among Candida albicans from animals, including efflux pump activity, ergosterol content and gene expression. For this purpose, 30 azole-resistant C. albicans strains from animals were tested for their antifungal susceptibility, according to document M27-A3, efflux pump activity by rhodamine 6G test, ergosterol content and expression of the genes CDR1, CDR2, MDR1, ERG11 by RT-qPCR. These strains were resistant to at least one azole derivative. Resistance to fluconazole and itraconazole was detected in 23 and 26 strains respectively. Rhodamine 6G tests showed increased activity of efflux pumps in the resistant strains, showing a possible resistance mechanism. There was no difference in ergosterol content between resistant and susceptible strains, even after fluconazole exposure. From 30 strains, 22 (73.3%) resistant animal strains overexpressed one or more genes. From this group, 40.9% (9/22) overexpressed CDR1, 18.2% (4/22) overexpressed CDR2, 59.1% (13/22) overexpressed MDR1 and 54.5% (12/22) overexpressed ERG11. Concerning gene expression, a positive correlation was observed only between CDR1 and CDR2. Thus, azole resistance in C. albicans strains from animals is a multifactorial process that involves increased efflux pump activity and the overexpression of different genes.


Handling S/MAR vectors.
Nonviral episomal vectors represent attractive alternatives to currently used virus-based expression systems. In the late 1990s, it was shown that a plasmid containing an expression cassette linked to a scaffold/matrix attached region (S/MAR) replicates as a low copy number episome in all cell lines tested, as well as primary cells, and can be used for the genetic modification of higher animals. Once established in the cell, the S/MAR vector replicates early during S-phase and, in the absence of selection, is stably retained in the cells for an unlimited period of time. This vector can therefore be regarded as a minimal model system for studying the epigenetic regulation of replication and functional nuclear architecture. In theory, this construct represents an almost "ideal" expression system for gene therapy. In practice, S/MAR-based vectors stably modify mammalian cells with efficiencies far below those of virus-based constructs. Consequently, they have not yet found application in gene therapy trials. Furthermore, S/MAR vector systems are not trivial to handle and several critical technical issues have to be considered when modifying these vectors for various applications.


Bleomycin-induced pulmonary fibrosis is attenuated by a monoclonal antibody targeting HER2.
The importance of HER2/HER3 signaling in decreasing the effects of lung injury was recently demonstrated. Transgenic mice unable to signal through HER2/HER3 had significantly less bleomycin-induced pulmonary fibrosis and showed a survival benefit. Based on these data, we hypothesized that pharmacological blockade of HER2/HER3 in vivo in wild-type mice would have the same beneficial effects. We tested this hypothesis in a bleomycin lung injury model using 2C4, a monoclonal antibody directed against HER2 that blocks HER2/HER3 signaling. The administration of 2C4 before injury decreased the effects of bleomycin at days 15 and 21 after injury. HER2/HER3 blockade resulted in less collagen deposition (362.8 +/- 37.9 compared with 610.5 +/- 27.1 microg/mg; P = 0.03) and less lung morphological changes (injury score of 1.99 +/- 1.55 vs. 3.90 +/- 0.76; P < 0.04). In addition, HER2/HER3 blockade resulted in a significant survival advantage with 50% vs. 25% survival at 30 days (P = 0.04). These results confirm that HER2 signaling can be pharmacologically targeted to reduce lung fibrosis and remodeling after injury.


The Seismic Shift in End-of-Life Care: Palliative Care Challenges in the Era of Medical Assistance in Dying.
Background: Concerns regarding personal, professional, administrative, and institutional implications of medical assistance in dying (MAiD) are of particular interest to palliative and hospice care providers (PHCPs), who may encounter additional moral distress and professional challenges in providing end-of-life (EOL) care in the new legislative and cultural era. Objective: To explore PHCPs' encountered challenges and resource recommendations for caring for patients considering MAiD. Design: Qualitative thematic analysis of audio-recorded semistructured interviews with PHCPs. Setting/Subjects: Multidisciplinary PHCPs in acute, community, residential, and hospice care in Vancouver, Canada, with experience supporting patients who have made MAiD inquiries or requests. Measurements: Interviews were deidentified, transcribed verbatim, and coded by four researchers using a common coding scheme. Key themes were analyzed. Results: Twenty-six PHCP participants included physicians (n = 7), nurses (n = 12), social workers (n = 5), and spiritual health practitioners (n = 2). Average interview length was 52 minutes (range 35-90). Analysis revealed four broad challenges associated with providing EOL care after MAiD legalization: (1) moral ambiguity and provider distress, (2) family distress, (3) interprofessional team conflict, and (4) impact on palliative care. Participants also recommended three types of resources to support clinicians in delivering quality EOL care to patients contemplating MAiD: (1) education and training, (2) pre- and debriefing for team members, and (3) tailored bereavement support. Conclusions: PHCPs encountered multilevel MAiD-related challenges, but noted improvement in organizational policies and coordination. Resources to enhance training, pre- and debriefing, and tailored bereavement may further support PHCPs in providing high-quality EOL care as they navigate the legislative and cultural shifts.


Susceptibility of Aedes aegypti (Diptera: Culicidae) to Acanthamoeba polyphaga (Sarcomastigophora: Acanthamoebidae).
To date there is no report on mosquitoes infected with free-living amoebae. For this reason, the aim of this study was to verify if Aedes aegypti could be susceptible to Acanthamoeba polyphaga under laboratory conditions, so trophozoites were offered as a unique food resource for larvae of first instar. The results show that those amoebae are able to infect and colonize the mosquito gut and could be re-isolated of all stages of the mosquito (larvae, pupae, and adults).